Ferroptosis-related protein biomarkers for diagnosis, differential diagnosis, and short-term mortality in patients with sepsis in the intensive care unit.

BACKGROUND: Sepsis is a disease with high mortality caused by a dysregulated response to infection. Ferroptosis is a newly discovered type of cell death. Ferroptosis-related genes are involved in the occurrence and development of sepsis. However, research on the diagnostic value of ferroptosis-related protein biomarkers in sepsis serum is limited. This study aims to explore the clinical value of Ferroptosis-related proteins in diagnosing sepsis and predicting mortality risk. METHODS: A single-center, prospective, observational study was conducted from January to December 2023, involving 170 sepsis patients, 49 non-septic ICU patients, and 50 healthy individuals. Upon ICU admission, biochemical parameters, GCS, SOFA, and APACHE II scores were recorded, and surplus serum was stored at -80°C for biomarker analysis via ELISA. Diagnostic efficacy was evaluated using ROC curve analysis. RESULTS: Baseline serum levels of ACSL4, GPX4, PTGS2, CL-11, IL-6, IL-8, PCT, and hs-CRP significantly differed among sepsis, non-septic, and healthy individuals (all p-value < 0.01). ACSL4, GPX4, PTGS2, IL-6, IL-8, PCT, and hs-CRP demonstrated high diagnostic and differential diagnostic performance (AUC: 0.6688 to 0.9945). IL-10 and TNF-α showed good diagnostic performance (AUC = 0.8955 and 0.7657, respectively). ACSL4 (AUC = 0.7127) was associated with predicting sepsis mortality. Serum levels of ACSL4, CL-11, and IL-6 above the cut-off value were associated with shorter survival times. ACSL4 levels were positively correlated with SOFA (Rho = 0.354, p-value < 0.0001), APACHE II (Rho = 0.317, p-value < 0.0001), and septic shock (Rho = 0.274, p-value = 0.003) scores but negatively correlated with the GCS score (Rho = -0.218, p-value = 0.018). GPX4 levels were positively correlated with SOFA (Rho = 0.204, p-value = 0.027) and APACHE II (Rho = 0.233, p-value = 0.011) scores. CONCLUSION: ACSL4 and GPX4 have strong diagnostic and differential diagnostic value in sepsis, including the ability to predict 28-day mortality in sepsis patients, and may become new potential serum markers for the diagnostic and differential diagnostic of sepsis.